Even after considerable advances in the field of epilepsy treatment, convulsions are inefficiently controlled by standard drug therapy. Herein, a series of pyrimidine-carbothioamide derivatives 4(a-t) was designed as anticonvulsant agents by doing some important structural modifications in well-known anticonvulsant drugs. Two classical animal models were used for the in vivo anticonvulsant screening, maximum electroshock seizure (MES) and subcutaneous pentylenetetrazole (scPTZ) models; followed by motor impairment study by rotarod method. The most active compound 4g effectively suppressed seizure effect in both the animal models with median doses of 15.6 mg/kg (MES ED50), 278.4 mg/kg (scPTZ ED50) and 534.4 mg/kg (TD50) with no sign of neurotoxicity. Furthermore, in vitro GABA-AT enzyme activity assay of 4g showed inhibitory potency (IC50) of 12.23 μM. The docking study also favored the animal studies.